KIF1A, a member of kinesin-3 motors, plays a pivotal role in anterograde axonal transport of synaptic vesicles (SVs). We have shown that the CC1-FHA tandem of KIF1A forms a stable dimer that is crucial for both the dimerization and activation of the motor. However, it remains to be determined whether the CC1-FHA dimer is essential for KIF1A-mediated axonal transport in vivo. Here, we use Caenorhabditis elegans as the model organism to probe the in vivo function of the CC1-FHA dimer. Disruption of the CC1-FHA dimer severely impairs the KIF1A-mediated regulation of the locomotion and pumping behavior of C. elegans and exerts a significant impact on KIF1A-mediated axonal SV transport. Thus, together with previous structural and biochemical studies, the in vivo data presented in this study firmly establish the essential role of the CC1-FHA dimer for KIF1A-mediated neuronal transport.
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